Structural basis for substrate specificity of the alpha-D-phosphohexomutase superfamily

Abstract only availablePhosphoacetylglucosamine mutase (PAGM) is a human enzyme that is the key to the formation of the essential metabolite UDP-N-acetylglucosamine. Bacterial phosphoglucomutase (PGM) from Acetobacter xylinum catalyzes the interconversion of glucose 1-phosphate and glucose 6-phosphate. PAGM and PGM are members of the alpha-D-phosphohexomutase superfamily which all catalyze intramolecular phosphoryl transfer on sugar substrates. These two analogs are similar in their mechanism, but dissimilar in their substrate specificity, not only to each other, but also to other well characterized (structurally and mechanistically) members of their superfamily. Protein expression and purification techniques were used to attempt to produce crystals to determine the three dimensional structures of human PAGM and bacterial PGM by X-ray diffraction in order to clarify the structural explanation for substrate specificity within the alpha-D-phosphohexomutase superfamily.Life Sciences Undergraduate Research Opportunity Progra

Density-dependent and landscape effects upon estuary rearing in Chinook salmon: insights from long-term monitoring in four Puget Sound estuaries

Juvenile Chinook salmon are well known for utilizing estuarine habitats within the tidal delta for rearing during outmigration. Several studies have linked population responses to availability of estuary habitat, and support the hypothesis that estuarine habitats are vital rearing areas for juvenile Chinook salmon. However, these coarse-scale studies provide little insight on how specific estuarine habitats contribute to rearing potential for salmon. We integrate long-term monitoring data from four estuaries of Puget Sound (Nooksack, Skagit, Snohomish, and Nisqually) to examine whether 1) Chinook populations in these rivers are limited by restricted estuary habitat, 2) hatchery releases can influence density dependent relationships in estuaries, 3) highly connected sites support higher densities of salmon, and 4) different habitat types support higher rearing densities of Chinook salmon. Across sampling locations within estuary systems, average annual rearing densities varied over four orders of magnitude. We found strong support for density dependence, habitat type, landscape connectivity, and hatchery release numbers influencing rearing densities, although all factors were not necessarily as important within each system, and effects of habitat type were particularly variable. Further work using bioenergetics models suggest that habitat-dependent variation in temperature can strongly influence growth in different systems, and that multiple habitats are likely important to provide suitable habitat for extended estuary rearing. These analyses are useful for determining the relative contribution of connectivity, cohort population size, and local habitat conditions for growth potential of Chinook salmon using estuarine habitats at early life stages, and shed light on likely impacts of climate change upon rearing conditions

Library Publishing Research Agenda

This publication is an exploration of areas in which research is needed to support practice in the field of library publishing. The Research Agenda offers exploratory overviews of six topics (assessment, labor, accessibility, non-traditional research outputs, peer review, and partnerships), each of which includes a summary, potential research questions, and a list of relevant resources. This publication will be of interest to anyone conducting or interested in conducting research in the field. The Research Agenda was authored by LPC’s Research Committee with input from the LPC community. HTML versio

Tibial Loading Increases Osteogenic Gene Expression and Cortical Bone Volume in Mature and Middle-Aged Mice

There are conflicting data on whether age reduces the response of the skeleton to mechanical stimuli. We examined this question in female BALB/c mice of different ages, ranging from young to middle-aged (2, 4, 7, 12 months). We first assessed markers of bone turnover in control (non-loaded) mice. Serum osteocalcin and CTX declined significantly from 2 to 4 months (p<0.001). There were similar age-related declines in tibial mRNA expression of osteoblast- and osteoclast-related genes, most notably in late osteoblast/matrix genes. For example, Col1a1 expression declined 90% from 2 to 7 months (p<0.001). We then assessed tibial responses to mechanical loading using age-specific forces to produce similar peak strains (−1300 µε endocortical; −2350 µε periosteal). Axial tibial compression was applied to the right leg for 60 cycles/day on alternate days for 1 or 6 weeks. qPCR after 1 week revealed no effect of loading in young (2-month) mice, but significant increases in osteoblast/matrix genes in older mice. For example, in 12-month old mice Col1a1 was increased 6-fold in loaded tibias vs. controls (p = 0.001). In vivo microCT after 6 weeks revealed that loaded tibias in each age group had greater cortical bone volume (BV) than contralateral control tibias (p<0.05), due to relative periosteal expansion. The loading-induced increase in cortical BV was greatest in 4-month old mice (+13%; p<0.05 vs. other ages). In summary, non-loaded female BALB/c mice exhibit an age-related decline in measures related to bone formation. Yet when subjected to tibial compression, mice from 2–12 months have an increase in cortical bone volume. Older mice respond with an upregulation of osteoblast/matrix genes, which increase to levels comparable to young mice. We conclude that mechanical loading of the tibia is anabolic for cortical bone in young and middle-aged female BALB/c mice

THE METABOLIC MAP OF THE PATHOMECHANISM AND TREATMENT OF PGM1-CDG

status: publishe